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Subclinical Left Ventricular Dysfunction During Chemotherapy Martin Nicol, 1 Mathilde Baudet 1 and Alain Cohen-Solal 1,2 1. Lariboisiere/Saint Louis Hospital, Cardiology Department, Paris, France; 2. UMR-S942 (BioCANVAS), Paris Diderot University, Paris, France

Abstract Subclinical left ventricular dysfunction is the most common cardiac complication after chemotherapy administration. Detection and early treatment are major issues for better cardiac outcomes in this cancer population. The most common definition of cardiotoxicity is a 10-percentage point decrease of left ventricular ejection fraction (LVEF) to a value <53%. The myocardial injury induced by chemotherapies is probably a continuum starting with cardiac biomarkers increase before the occurence of a structural myocardial deformation leading to a LVEF decline. An individualised risk profile (depending on age, cardiovascular risk factors, type of chemotherapy, baseline troponin, baseline global longitudinal strain and baseline LVEF) has to be determined before starting chemotherapy to consider cardioprotective treatment. To date, there is no proof of a systematic cardioprotective treatment (angiotensin-converting enzyme inhibitor and/or betablocker) in all cancer patients. However, early cardioprotective treatment in case of subclinical left ventricular dysfunction seems to be promising in the prevention of cardiac events.

Keywords Left ventricular dysfunction, cardio-oncology, cardiotoxicity Disclosure: The authors have no conflicts of interest to declare Received: 22 July 2018 Accepted: 29 November 2018 Citation: Cardiac Failure Review 2019;5(1):31–6. DOI: Correspondence: Alain Cohen-Solal, 2 Rue Ambroise-Paré, Lariboisière Hospital, 75010 Paris, France. E: Open Access: This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

Advances in the early detection and treatment of cancer have improved overall survival in cancer patients. Nevertheless, cardiovascular diseases appear as the major cause of morbidity and mortality among cancer survivors.1 Left ventricular (LV) dysfunction and/or heart failure are the most common cardiovascular complications after administration of chemotherapies. The term ‘cardiotoxicity’ is generally used to refer to LV dysfunction. The two main anticancer agents responsible for LV dysfunction are anthracyclines and targeted therapies (tyrosine kinase inhibitor, anti-human epidermal growth factor receptor 2, anti-vascular endothelial growth factor, proteasome inhibitors). Recently, immune fulminant myocarditis was reported with the use of checkpoint immune inhibitors (anti-programmed cell death protein 1, anti-programmed cell death ligand 1, anti-cytotoxic T lymphocyte-associated protein 4), suggesting new cardiotoxicity pathways.2 LV dysfunction remains asymptomatic for a long time, but once symptomatic, the prognosis is one of the poorest in the heart failure population.3 The challenge is then to detect myocardial toxicity before symptomatic heart failure. The aim of this review was to define subclinical LV dysfunction during chemotherapy, to identify the best early strategy for cardiodetection, and to summarise the studies’ results about a cardioprotective treatment for cancer patients with subclinical LV dysfunction.

Definition of Left Ventricular Dysfunction Induced by Cardiotoxic Chemotherapies LV dysfunction induced by cardiotoxic chemotherapies is defined by a decrease in left ventricular ejection fraction (LVEF) of >10 percentage points to a value <53%.4 To detect early myocardial damage before a


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change in LVEF, an increase in biomarkers levels (mainly troponin I; TnI) and a decrease of >15% of the global longitudinal strain are useful tools. According to the European Society of Cardiology, LVEF assessment can be performed by echocardiography (attempting to favour 3D LVEF), cardiac nuclear imaging and cardiac MRI.2,5

Detecting Subclinical Left Ventricular Dysfunction Before LVEF Decrease Identifying High-risk Patients The paediatric population (aged <18 years) or older patients (aged >65 years) have an increased risk of cardiotoxicity. Moreover, cardiovascular risk factors (arterial hypertension, diabetes, hypercholesterolaemia or family history of cardiovascular disease), current myocardial disease, previous cardiotoxic cancer therapies or lifestyle risk factors (smoking, alcohol, sedentary habits, obesity) are associated with LV dysfunction related to cancer therapy. A careful baseline evaluation and cardiac monitoring during and after treatment of these patients is recommended.5

Monitoring Using Cardiac Biomarkers Troponins (Troponin I and Troponin T) Cardinale et al. measured TnI in 703 breast cancer patients before chemotherapy, 3 days after and 1 month after chemotherapy, and showed that elevated TnI was able to predict cardiovascular events (cardiovascular mortality, pulmonary oedema, LVEF <25%, arrhythmias).6 Patients with an early or persistent increase of TnI ≥0.08 ng/ml had a higher incidence of cardiac events (37% and 84% respectively; p<0.001).

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